Treatment recommendations and results reported for the management of staghorn calculi are highly variable. In an attempt to provide a more objective means to compare treatment results for staghorn renal calculi, stone burden as measured by stone surface area was used. Stone surface area was determined by computer analysis. A total of 380 cases of staghorn calculi treated at the same institution was evaluated. Treatment consisted of initial percutaneous nephrostolithotomy with or without extracorporeal shock wave lithotripsy (ESWL*) in 298 cases and ESWL monotherapy in 82. When considered as a group, the overall stone-free rate for initial percutaneous nephrostolithotomy (mean surface area 1,378.3 mm.2) was 84.2% compared to 51.2% (p less than 0.0001) for ESWL monotherapy (mean surface area 693.4 mm.2). For staghorn calculi smaller than 500 mm.2 a stone-free rate of 94.4% was achieved in the percutaneous nephrostolithotomy with or without ESWL group compared to 63.2% for ESWL monotherapy (p = 0.0214). For calculi of 501 to 1,000 mm.2 the stone-free rates were 86% and 45.7%, respectively (p less than 0.0001). When stone surface area exceeded 1,000 mm.2 the stone-free rate for percutaneous nephrostolithotomy with or without ESWL was 82.4% but it was only 22.2% for ESWL monotherapy (p = 0.0002). Overall, when adjusted for stone surface area the odds of being stone-free were more than 8 times higher for initial percutaneous nephrostolithotomy versus ESWL monotherapy (odds ratio = 8.36, p less than 0.0001). While percutaneous nephrostolithotomy with or without ESWL appears to be the procedure of choice for most staghorn stones, ESWL monotherapy may have a role for some stones smaller than 500 mm.2. In 12 such cases associated with a nondilated renal collecting system (mean surface area 380.5 mm.2) a stone-free rate of 91.7% was achieved. The number of procedures required to complete therapy was higher in the initial percutaneous nephrostolithotomy group (2.8 versus 2.1, p less than 0.0001). Although complications were more common in the ESWL monotherapy group (manifested as obstruction in 30.5%), bleeding requiring blood transfusion was more frequent in the initial percutaneous nephrostolithotomy group (9.4%).